The R576 IL-4 receptor α allele correlates with asthma severity

• Published in: Journal of allergy and clinical immunology 1999-11, Vol.104 (5), p.1008-1014
• Main Authors: Rosa-Rosa, Lillian, Zimmermann, Nives, Bernstein, Jonathan A., Rothenberg, Marc E., Khurana Hershey, Gurjit K.
• Format: Article
• Language: English
• Subjects: Adult; Alleles; Allergic diseases; Asthma; Asthma - epidemiology; Asthma - genetics; Asthma - immunology; Asthma - physiopathology; atopic hypersensitivity; Biological and medical sciences; bronchial hyperreactivity; Cell Line, Transformed; genetic predisposition to disease; Genetic Variation; Homozygote; Humans; IL-13; IL-4; Immunopathology; interleukin 4 receptors; Medical sciences; Polymerase Chain Reaction - methods; Polymorphism, Restriction Fragment Length; Polymorphism, Single-Stranded Conformational; Prospective Studies; Receptors, Interleukin-4 - genetics; Respiratory and ent allergic diseases
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/S0091-6749(99)70082-5

Background: Atopic disorders, including asthma, are very prevalent, affecting up to 40% of populations, and their incidence is on the rise. Although environmental factors are important in the development of atopy, there is a strong genetic predisposition. Several genes and chromosomal regions have been linked to atopy and asthma, supporting the polygenic nature of these disorders. IL-4 and IL-13 are T H2 cytokines with numerous activities that contribute to allergic inflammation and asthma. Both IL-4 and IL-13 use the IL-4 receptor α chain (IL-4Rα) as a component of their respective receptor systems. Allelic variants of IL-4Rα have been reported, and the R576IL-4Rα allele was recently shown to be a risk factor for atopy. Objective: We sought to determine whether the R576 allele was associated with the prevalence or clinical severity of asthma. Methods: We developed a rapid, reliable, PCR-based assay to screen individuals for the R576IL-4Rα allele and used this assay to genotype prospectively recruited individuals with asthma (n = 149) and control subjects (n = 57). Results: There was a strong association of R576IL-4Rα with the prevalence and clinical severity of asthma. In a prospective cohort, homozygosity for R576 was significantly increased in individuals with asthma (n = 149, P = .03; relative risk 8.2) compared with controls (n = 57). Furthermore, 1 or 2 copies R576IL-4Rα correlated with asthma severity establishing a genotype-phenotype relationship and suggesting a gene dosage effect. Conclusions: Thus R576IL-4Rα acts as an allergic asthma susceptibility and disease-modifying gene and may serve as a clinically useful marker of asthma severity. (J Allergy Clin Immunol 1999;104:1008-14.)